1-acyloxy-4-hydroxy-2-alkoxy-4a-methyl-1, 4, 4a, 5, 8, 8a-hexahydronaphthalenes and their production



United States Patent 1-ACYLOXY-4- HYDROXY-Z-ALKOXY- la METHYL-1,4,4a,5,8,Sa-HEXAHYDRONAPHTHALENES AND THEIR PRODUCTION Ferdinand C.Meyer and Angelo J. Speziale, Kirkwood, Mo., assignors to MonsantoChemical Company, St. Louis, Mo., a corporation of Delaware No Drawing.Application December 14, 1953, Serial No. 398,198

11 Claims. (Cl. 260-488) This invention relates to new and usefulmono-carboxylic acid esters of dihydroxy substituted carbocyclicbicyclic compounds. More specifically this invention relates tol-acyloxy 4 hydroxy-2-allcoxy-4a-methyl-1,4,4a,5,8,Sa-hexahydronaphthalenes, which mono-esters may berepresented by the structural formula HO OH! where R is hydrogen or ahydrocarbon radical such as the alkyl, aralkyl, cycloalkyl, aryl, andalkaryl radicals, and where R is a short chain alkyl radical such asmethyl, ethyl, propyl, butyl, amyl, etc.

It will be obvious to those skilled in the art that the new compounds ofthis invention contain four optically active carbon atoms. As a resultthereof these compounds may exist in sixteen optically active forms orare useful intermediates in the synthesis of steroids (J. A. C. S. 74,September 1952, p. 4223). The conversion of the trans esters to thecorresponding trans bicyclic ketones may be represented schematically asfollows, R and R having the same significance as aforedescribed,

HO OH:

acid

hydrolysis The new esters of this invention are prepared by thereduction of the 4-keto substituent of the corresponding1-acyloxy-4-keto-2-alkoxy-4a-methyl-1,4,4a,5,8,8a hexahydronaphthalene,which compounds are described and claimed in co-pending applicationSerial No. 314,416, filed October 11, 1952, employing an aluminumalkoxide of the formula Al(OR")a where R is a short chain alkyl radicalsuch as ethyl, propyl, sec. butyl, etc. The preferred alkoxide isaluminum isopropoxide. Although the quantity of aluminum alkoxide mayvary widely, ordinarily its molar ratio toth e 4-keto reactant will bein the range of about 1 to 3:1. It is preferred that the molar ratio bein the range of about 2 of aluminum alkoxide to 1 of the 4-ketoreactant.

In general anhydrous isopropanol will be employed as the solvent in thepreparation of the new esters, however,

other anhydrous inert organic solvents may be employed, for exampleisobutyl alcohol, ethyl alcohol, toluene, xylene and the like as well asmixtures thereof. Ordinarily the temperature at which the reaction isconducted Example I To a suitable reaction vessel containingapproximately 79 parts by weight of anhydrous isopropanol andapproximately 16.7 parts by weight of dl-trans-lrbutyryloxy- 4-keto 2methoxy-4a-methyl-1,4,4a,5,8,8a-hexahydronaphthalene (substantially 0.06mol) isadded and intimately mixed 16.3 parts by weight of aluminumisopropoxide (substantially 0.08.-mol). The mix is then refiuxed whilepermitting the acetone formed to slowly distil 10E. During the refluxingperiod (about 17 hours) approximately 79 parts by weight of anhydrousisopropanol is added. The reaction mix is cooled to about 5-10" C. andthereto is added 79 parts by weight of a mixture of isopropanol andwater in a weight ratio of 4:1. The precipitated aluminum hydroxide isfiltered off and the collected residue washed with 158 parts by weightof 3 anhydrous isopropanol. The washings and original filtrate arecombined and subjected to vacuum distillation. The light colored oil (a77% of theory yield) is dl-trans- 1-=butyryloxy 4 hydroxy 2 'nethoxy4a-methyll,4,4a,5,8,8a-hexahydronaphthalene.

Example 11 To a suitable reaction vessel containing approximately 86parts by weight of anhydrous toluene and approxi-' mately parts byweight of dZ-trans-1-acetyloxy-4-keto- 2-methoxy-4a-methyl l,4,4a,5,8,8ahexahydronaphthalene (substantially 0.04 mol) is added and intimatelymixed 16.3 parts by weight of aluminum isopropoxide (substantially 0.08mol). The mix is then refluxed while permitting the acetone formed toslowly distil oif. The reaction mix is cooled to about 5l0 C. andthereto is added 50 parts by weight of water and 43 parts by Weight oftoluene. The precipitated aluminum hydroxide is filtered ofi and thecollected residue Washed with 160 parts by weight of methanol. Thewashings and original filtrate are combined and subjected to vacuumdistillation. The oily residue (a 53% of theory yield) isdltrans-l-acetyloxy 4 hydroxy 2 -methoxy-4a-methyl-1,4,4a,5,8,8a-hexahydronaphthalene.

In addition to the esters prepared in the preceding examples, thefollowing examples are further illustrations of compounds coming withinthe scope of this invention:

1-n-propanoyloxy-4-hydroxy 2 methoxy-4a-methyl-1,4,4a,5,8,Sa-hexahydronaphthalene.

l-isobutyryloxy 4 hydroxy 2ethoxy-4anethyll,4,4a,5,8,Sa-hexahydronaphthalene.

l-n-pentanoyloxy 4hydroxy-Z-methoxy-4a-methyll,4,4a,5,8,Sa-hexahydronaphthalene.

l-(2-ethyl-hexanoyloxy) 4hydroxy-2-n-propoxy-4amethyl-1,4,4a,5,8,8a-hexahydronaphthalene.

1-n-octanoyl0xy-4-hydroxy 2 methoxy-4a-methyl- Z. ,4,4a,5 8,8a-hexahydronaphtha1ene.

l-n-decanoyloxy 4-hydroxy 2 methoxy-4a-methyl-1,4,4a,5,8,8a-hexahydronaphthalene.

l-n-octadecanoyloxy 4-hydroxy-2-methoxy-4a-methy1-1,4,4a,5,8,Sa-hexahydronaphthalene.

l-naphthoyloxy-4-hydroxy 2 methoxy 4a. methyl- 1 ,4,4a,5,8,8a-hexahydronaphthalene.

l-formyloxyl-hydroxy 2 n butoxy 4a methyl- 1 ,4,4a,5,8,8a-hexahydronaphthalene.

l-caproyloxy 4 hydroxy 2methoxy-4a-methyll,4,4a,5,8,8a-hexahydronaphthalene.

l-benzoyloxy 4 hydroxy 2 ethoxy-4a-methyl-1,4,4a,5,8,8a-hexahydronaphthalene.

l-p-toluyloxy 4hydroxy-2-methoxy-4a-methyll,4,4a,5,8,8a-hexahydronaphthalene.

l-cyclohexanoyloxy 4 hydroxy-2-ethoxy-4a-methyll,4,4a,5,8,Sa-hexahydronaphthalene.

l-phenylacetyloxy 4 hydroxy-Z-methoxy-4a-methyll ,4,4a,5 8 ,8ahexahydronaphtha1ene.

l-phenylpropanoyloxy-4-hydroxy-2-methoxy-4a-methy1- l ,4,4a,5 8 ,8a-hexahydronaphthalene.

The new esters of this invention where R is an alkane radical containingl-l7 carbon atoms represent a preferred embodiment of this invention. Ofthis preferred embodiment the esters wherein R is an alkane radicalcontaining 3-7 carbon atoms have been found particularly useful.

Although the preceding examples have described certain specificembodiments of this invention both as to the nature of the novel estersand their method of preparation, it is to be understood that substantialvariations obvious to those skilled in the art in the reactants andreaction conditions may be made without departing from the spirit orscope of this invent-ion.

What is claimed is:

1. As new compounds l-acyloxy-2-alkoxy-4-hydroxy- 4a methyl--l,4,4a,5,8,Sa-hexahydronaphthalenes of the structural formula HO OH:

RIO l where R is a member of the group consisting of hydrogen andhydrocarbon radicals and where R is a short chain alkyl radical.

2. As new compounds l-acyloxy-2-methoxy-4-hydroxyla-methyl 1,4,4a,5,8,8ahexahydronaphthalenes of the structural formula HO CH3 CHaO I (I? CHwhere R is an alkyl radical containing from 1 to 17 oarbon atoms with analuminum short-chain alkoxide.

10. The process of claim 9 employing a reaction temperature in the rangefrom about 40 C. to C.

11. The process of making the ester of claim 9 which comprises refluxingdl-trans l n-butyryloxy-4-keto-2- methoxy-4a-methyl-l,4,4a,5,8,8ahexahydronaphthalene with aluminum isopropoxide in isopropanol.

References Cited in the file of this patent UNITED STATES PATENTSWoodward Mar. 16, 1954 OTHER REFERENCES Woodward et al.: I. Am. Chem.Soc., 74 (1952), 4223.

1. AS NEW COMPOUNDS 1-ACYLOXY-2-ALKOXY-4-HYDROXY4A-METHYL--1,4,4A,5,8,8A-HEXAHYDRONAPHTHALENES OF THE STRUCTURAL FORMULA